Two-Year Outcomes of Primary Arthroscopic Surgery in Patients with Femoroacetabular Impingement: A Comparative Study of Labral Repair and Labral Reconstruction.

BACKGROUND: Labral repair has become the preferred method for the arthroscopic treatment of acetabular labral tears that are associated with femoroacetabular impingement (FAI) resulting in pain and dysfunction. Labral reconstruction is performed mainly in revision hip arthroscopy but can be utilized in the primary setting for absent or calcified labra. The purpose of this study was to compare the minimum 2-year patient-reported outcomes (PROs) and risk of revision or conversion to arthroplasty between primary labral reconstruction and primary labral repair. METHODS: Patients with FAI who underwent primary hip arthroscopy with labral repair or reconstruction performed by the senior author between 2006 and 2018 were identified from a prospectively enrolled patient outcome registry. Exclusion criteria included confounding injuries, dysplasia, prior ipsilateral hip surgery, or a joint space of <2 mm. Patients who were 18 to 80 years old were eligible for inclusion. Multiple regression with inverse propensity score weighting was conducted to estimate the average treatment effect in the treated (ATT) for labral reconstruction versus labral repair with respect to postoperative PROs and the likelihood of subsequent surgery (revision hip arthroscopy or conversion to arthroplasty). PRO end points included the Hip Outcome Score Activities of Daily Living subscale (HOS-ADL), modified Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index total score (WOMAC), 12-Item Short Form Health Survey Physical Component Summary score (SF-12 PCS), and patient satisfaction. RESULTS: A total of 150 hips undergoing primary labral reconstruction and 998 hips undergoing primary labral repair were included. The median follow-up time was 5.3 years in the reconstruction group and 5.8 years in the repair group. Compared with labral repair, labral reconstruction was associated with a higher risk of conversion to total hip arthroplasty (THA) (20% versus 7%; adjusted odds ratio, 3.2; 95% confidence interval [CI], 1.2 to 8.8; p = 0.024). Inverse propensity score-weighted multiple regression estimated a significant negative effect of labral reconstruction, relative to labral repair, on the postoperative values for the HOS-ADL (ATT, -3.3; 95% CI, -5.8 to -0.7; p = 0.012) and WOMAC (ATT, 2.6; 95% CI, 0.1 to 5.2; p = 0.044). CONCLUSIONS: Compared with primary labral reconstruction, primary labral repair resulted in better postoperative HOS-ADL and WOMAC values and decreased conversion to THA. These findings were demonstrated in both the unadjusted group comparisons and multivariable modeling. These data support the use of labral repair in the primary setting of labral tears and the reservation of labral reconstruction for more advanced labral pathology or for revision cases. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

How Strong Is the Ligamentum Teres of the Hip? A Biomechanical Analysis.

BACKGROUND: Intraarticular hip pain represents a substantial clinical challenge, with recent studies implicating lesions in the ligamentum teres as potential contributors. Even more so, damage to the ligamentum teres is particularly prevalent among young patients undergoing joint-preserving interventions. Although several studies have investigated the biomechanical attributes of the ligamentum teres, inconsistencies in reported findings and reliance on cadaveric or animal models have raised concerns regarding the extrapolation of results to clinical practice. Furthermore, there is a lack of research examining ligamentum teres biomechanics specifically within the relevant patient cohort-individuals who benefit from joint-preserving surgical interventions. QUESTIONS/PURPOSES: We sought (1) to determine the biomechanical properties (ultimate load to failure, tensile strength, stiffness, and elastic modulus) of fresh-frozen ligaments from patients undergoing surgical hip dislocation, and (2) to identify patient-specific factors that are associated with them. METHODS: This was an institutional review board-approved study on intraoperatively harvested ligamentum teres from 74 consecutive patients undergoing surgical hip dislocation for joint preservation (August 2021 to September 2022). After the exclusion of patients with previous surgery, posttraumatic deformities, avascular necrosis, slipped capital femoral epiphysis, and Perthes disease, 31 ligaments from 31 patients were analyzed. The mean age of the study group was 27 ± 8 years, and 61% (19) of participants were male. The main indication for surgery was femoroacetabular impingement. Standardized AP pelvic and axial radiographs and CT scans were performed in all patients for better radiological description of the population and to identify associated radiological factors. The ligament was thoroughly transected at its origin on the fossa acetabuli and at the insertion area on the fovea capitis and stored at -20°C until utilization. Specimens were mounted to a materials testing machine via custom clamps that minimized slippage and the likelihood of failure at the clamp. Force-displacement and stress-strain curves were generated. Ultimate failure load (N), tensile strength (MPa), stiffness (N/mm), and elastic modulus (MPa) were determined. Using a multivariate regression analysis and a subgroup analysis, we tested demographic, degenerative, and radiographic factors as potential associated factors. RESULTS: The ligamentum teres demonstrated an ultimate load to failure of 126 ± 92 N, and the tensile strength was 1 ± 1 MPa. The ligaments exhibited a stiffness of 24 ± 15 N/mm and an elastic modulus of 7 ± 5 MPa. After controlling for potential confounding variables like age, fossa/fovea degeneration, and acetabular/femoral morphologies, we found that female sex was an independent factor for higher tensile strength, stiffness, and elastic modulus. Excessive femoral version was independently associated with lower load to failure (HR 122 [95% CI 47 to 197]) and stiffness (HR 15 [95% CI 2 to 27]). Damage to the acetabular fossa was associated with reduced load to failure (HR -93 [95% CI -159 to -27]). CONCLUSION: Overall, the ligamentum teres is a relatively weak ligament. Sex, degeneration, and excessive femoral version are influencing factors on strength of the ligamentum teres. The ligamentum teres exhibits lower strength compared with other joint-stabilizing ligaments, which calls into question its overall contribution to hip stability. CLINICAL RELEVANCE: Young patients undergoing hip-preserving surgery are the population at risk for ligamentum teres lesions. Baseline values for load to failure, tensile strength, elastic modulus, and stiffness are needed to better understand those lesions in this cohort of interest.

A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model.

Regeneration of hyaline cartilage in human-sized joints remains a clinical challenge, and it is a critical unmet need that would contribute to longer healthspans. Injectable scaffolds for cartilage repair that integrate both bioactivity and sufficiently robust physical properties to withstand joint stresses offer a promising strategy. We report here on a hybrid biomaterial that combines a bioactive peptide amphiphile supramolecular polymer that specifically binds the chondrogenic cytokine transforming growth factor ß-1 (TGFß-1) and crosslinked hyaluronic acid microgels that drive formation of filament bundles, a hierarchical motif common in natural musculoskeletal tissues. The scaffold is an injectable slurry that generates a porous rubbery material when exposed to calcium ions once placed in cartilage defects. The hybrid material was found to support in vitro chondrogenic differentiation of encapsulated stem cells in response to sustained delivery of TGFß-1. Using a sheep model, we implanted the scaffold in shallow osteochondral defects and found it can remain localized in mechanically active joints. Evaluation of resected joints showed significantly improved repair of hyaline cartilage in osteochondral defects injected with the scaffold relative to defects injected with the growth factor alone, including implantation in the load-bearing femoral condyle. These results demonstrate the potential of the hybrid biomimetic scaffold as a niche to favor cartilage repair in mechanically active joints using a clinically relevant large-animal model.

Murine Progeria Model Exhibits Delayed Fracture Healing with Dysregulated Local Immune Response.

Background: Bone fracture is one of the most globally prevalent injuries, with an estimated 189 million bone fractures occurring annually. Delayed union or nonunion occurs in up to 15% of fractures and involves the interruption or complete failure of bone continuity following fracture. Preclinical testing is essential to support the translation of novel strategies to promote improved fracture repair treatment, but there is a paucity of small animal models that recapitulate clinical attributes associated with delayed fracture healing. This study explores whether the Zmpste24 -/- (Z24 -/- ) knockout mouse model of Hutchinson-Gilford progeria syndrome presents with delayed fracture healing. Leveraging the previously characterized Z24 -/- phenotype of genomic instability, epigenetic changes, and fragility, we hypothesize that these underlying alterations will lead to significantly delayed fracture healing relative to age-matched wild type (WT) controls. Methods: WT and Z24 -/- mice received intramedullary fixed tibia fractures at ∼12 weeks of age. Mice were sacrificed throughout the time course of repair for the collection of organs that would provide information regarding the local (fracture callus, bone marrow, inguinal lymph nodes) versus peripheral (peripheral blood, contralateral tibia, abdominal organs) tissue microenvironments. Analyses of these specimens include histomorphometry, µCT, mechanical strength testing, protein quantification, gene expression analysis, flow cytometry for cellular senescence, and immunophenotyping. Results: Z24 -/- mice demonstrated a significantly delayed rate of healing compared to WT mice with consistently smaller fracture calli containing higher proportion of cartilage and less bone after injury. Cellular senescence and pro-inflammatory cytokines were elevated in the Z24 -/- mice before and after fracture. These mice further presented with a dysregulated immune system, exhibiting generally decreased lymphopoiesis and increased myelopoiesis locally in the bone marrow, with more naïve and less memory T cell but greater myeloid activation systemically in the peripheral blood. Surprisingly, the ipsilateral lymph nodes had increased T cell activation and other pro-inflammatory NK and myeloid cells, suggesting that elevated myeloid abundance and activation contributes to an injury-specific hyperactivation of T cells. Conclusion: Taken together, these data establish the Z24 -/- progeria mouse as a model of delayed fracture healing that exhibits decreased bone in the fracture callus, with weaker overall bone quality, immune dysregulation, and increased cellular senescence. Based on this mechanism for delayed healing, we propose this Z24 -/- progeria mouse model could be useful in testing novel therapeutics that could address delayed healing. The Translational Potential of this Article: This study employs a novel animal model for delayed fracture healing that researchers can use to screen fracture healing therapeutics to address the globally prevalent issue of aberrant fracture healing.

Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes.

Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro-inflammatory senescence-associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age-related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss. However, it is unknown if the percentage of senescent PBMCs associated with age-associated orthopedic decline could be used for potential diagnostic or prognostic use in orthopedics. Here, we report senescent cell detection using the fluorescent compound C12FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C12FDG+ PBMCs that is commensurate with increases in age and senescence-related serum biomarkers. Interestingly, C12FDG+ PBMCs and T cells also were found to be elevated in patients with mild to moderate osteoarthritis, a progressive joint disease that is strongly associated with inflammation. The percent of C12FDG+ PBMCs and age-related serum biomarkers were decreased in a small subgroup of study participants taking the senolytic drug fisetin. These results demonstrate quantifiable measurements in a large group of participants that could create a composite score of healthy aging sensitive enough to detect changes following senolytic therapy and may predict age-related orthopedic decline. Detection of peripheral senescence in PBMCs and subsets using C12FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.

Evaluating the Morphology of Unique Superficial Fissured Cartilage Lesions at the Femoral Head-Neck Junction in Patients with Femoroacetabular Impingement Syndrome.

Background: While an association between femoroacetabular impingement (FAI) and osteoarthritis (OA) has been reported, the mechanistic differences and transition between the 2 conditions is not fully understood. In FAI, cartilage lesions at the femoral head-neck junction can sometimes be visualized during hip arthroscopy. Purpose/Hypothesis: The purpose of this study was to describe a unique dimpled pattern of superficial fissured cartilage lesions on the femoral head-neck junction at impingement site in patients with FAI syndrome (FAIS) and to evaluate the clinical, histological, and genetic phenotype of this cartilage. We hypothesized that the cartilage lesions may indicate risk for, or predict occurrence of, OA. Study Design: Controlled laboratory study. Methods: Six hips (6 patients; mean age, 34.2 ± 12.9 years; range, 19-54 years) with dimpled or fissured cartilage were included among patients who underwent hip arthroscopy for treatment of FAIS from October 2020 through December 2021. This affected cartilage (dimple-pattern group) and normal cartilage (control group) on the femoral head-neck junction were collected from the same patients and evaluated for histological quantification by Mankin scores and expression of proteins related to cartilage degeneration (eg, matrix metalloproteinase [MMP]-1, MMP-2, MMP-3, MMP-10, and MMP-12, tissue inhibitor of metalloproteinase [TIMP]-1 and TMP-2, aggrecan neopepitope CS846, and hyaluronic acid [HA]) with the use of Milliplex Multiplex Assays. Results: All 6 hips were of the mixed FAI subtype. Preoperatively, 4 of 6 hips had Tönnis grade 1 radiographic changes, which was associated with greater femoral head chondral damage visualized intraoperatively. Mankin scores for the normal cartilage group and the dimple-pattern group were 0.67 ± 0.82 and 3.3 ± 0.82, respectively. Dimple pattern fissured cartilage showed a significant increase in Mankin score (P = .031) and a significant increase in protein expression of CS846 (P = .031) compared with normal cartilage. There were no significant differences in MMPs, TIMPs, or HA levels between the 2 groups. Conclusion: The dimple pattern fissured cartilage, compared to normal cartilage, showed histologically significant cartilage degeneration and a significant increase in protein expression of CS846, a biomarker for early OA. Clinical Relevance: This lesion serves as helpful visual indicator of early degeneration of the cartilage of femoral head-neck junction caused by FAIS.

Biomechanical Comparison Between Double-Row Repair and Soft Tissue Tenodesis for Treatment of Proximal Rectus Femoris Avulsions.

Background: Some patients with proximal rectus femoris (PRF) avulsions require surgical treatment after failed nonoperative treatment. There is no consensus on the superiority of suture anchor repair with the suture-bridge repair (SBR) technique versus tenodesis repair (TR) for PRF avulsions. Purpose: To compare the failure load and elongation at failure between SBR and TR and to compare the stiffness of these 2 repair techniques versus the native state. Study Design: Controlled laboratory study. Methods: Seven pairs of human cadaveric hemipelvises were dissected to the PRF and sartorius origins. Each specimen underwent preconditioning followed by a distraction test to determine the stiffness of the native specimen. One specimen of each pair received one of the repair methods (SBR or TR), while the other specimen in the pair received the other repair technique. After repair, each specimen underwent preconditioning followed by a pull to failure. The failure load, elongation at failure, stiffness, mode of failure, and stiffness as a percentage of the native state were determined for each repair. Results: The SBR group exhibited a stronger failure load (223 ± 51 N vs 153 ± 32 N for the TR group; P = .0116) and significantly higher stiffness as a percentage from the native state (70.4% ± 19% vs 33.8% ± 15.5% for the TR group; P = .0085). While the stiffness of the repair state in the SBR group (41.5 ± 9.4 N/mm) was not significantly different from that of the native state (66.2 ± 36 N/mm), the stiffness of the repair state in the TR group (20.3 ± 7.5 N/mm) was significantly lower compared with that of the native state (65.4 ± 22.1 N/mm; P < .001) and repair state in the SBR group (41.5 ± 9.4 N/mm; P = .02). The SBR group primarily failed at the repair site (71%), and the TR group primarily failed at the suture-sartorius interface (43%) and at the muscle (29%). Conclusion: SBR and TR specimens were significantly weaker than the native tendon. The stiffness of the SBR was equivalent to that of the native tendon, while TR was significantly less stiff than the native tendon. The SBR was superior to TR in terms of failure load, stiffness, and percentage stiffness from the native state. Clinical Relevance: SBR may be a better surgical option than TR to optimize failure load and stiffness for PRF avulsions.

Editorial Commentary: Iliotibial Band Autograft Is a Safe and Effective Technique for Hip Labral Reconstruction.

Hip labral reconstruction is indicated for hypoplastic, ossified, or irreparable labral tears in the primary and revision settings. Arthroscopic reconstruction for insufficient labral tissue requires advanced surgical techniques to restore hip biomechanics and re-establish the suction seal. With the growing number of arthroscopic hip procedures being performed, this is an increasingly familiar scenario. In our experience, the iliotibial band (ITB) autograft provides a safe and effective technique for labral reconstruction at 10-year clinical follow-up. Although the harvest requires an additional incision, the graft is incredibly versatile and can be harvested at any size to address the labral deficiency. Despite the concerns for donor-site morbidity, our extensive experience shows this is incredibly rare. In addition, concomitant pathology, such as greater trochanteric bursitis, can be addressed through this incision. Other grafts can be used for labral reconstruction, such as the indirect head of the rectus femoris tendon, but this is often limited to smaller labral defects less than 1 cm. ITB autograft shows excellent mid- to long-term outcomes, and second-look surgeries show excellent incorporation of the ITB autograft. And, in contrast to allograft, autograft tissue has demonstrated lower revision rates. The type of autograft used is per surgeon discretion based on experience and preference. In our hands, ITB is optimal due to proven effectiveness, durability, versatility, and limited donor-site morbidity.

Improved Functional Outcomes of Combined Hip Arthroscopy and Periacetabular Osteotomy at Minimum 2-Year Follow-Up.

PURPOSE: To evaluate patient-reported outcomes (PROs) and survivorship at minimum 2-year follow-up after combined hip arthroscopy and periacetabular osteotomy (PAO) performed in the setting of a single anesthetic event. METHODS: Patients who underwent combined hip arthroscopy (M.J.P.) and PAO (J.M.M.) between January 2017 and June 2020 were identified. Preoperative and minimum 2-year postoperative PROs including Hip Outcome Score-Activities of Daily Living (HOS-ADL), HOS-Sport, modified Harris Hip Score (mHHS), Western Ontario and McMaster Universities Osteoarthritis Index, 12-Item Short Form Survey Mental Component Scores (SF-12 MCS), and 12-Item Short Form Survey Physical Component Score were collected and compared in addition to revision rate, conversion to total hip arthroplasty (THA), and patient satisfaction. RESULTS: Twenty-four of 29 patients (83%) eligible for the study were available for 2-year minimum follow-up with a median follow-up time of 2.5 years (range, 2.0-5.0). There were 19 females and 5 males with mean age of 31 ± 12 years. Mean preoperative lateral center edge angle was 20° ± 5° and alpha angle was 71° ± 11°. One patient underwent reoperation for removal of a symptomatic iliac crest screw at 11.7 months after operation. Two patients, a 33-year-old woman and a 37-year-old man, were converted to THA at 2.6 and 1.3 years, respectively, following the combined procedure. Both patients had a Tönnis grade of 1 on radiographs, as well as bipolar Outerbridge grade III/IV defects requiring microfracture of the acetabulum. For patients who did not convert to THA (n = 22), there was significant improvement from before to after surgery for all scores (P < .05) except SF-12 MCS. The minimal clinically significant difference and patient-acceptable symptom state rates for HOS-ADL, HOS-Sport, and mHHS were 72%, 82%, 86%, and 95%, 91%, and 95%, respectively. Median patient satisfaction was 10 (range, 4 to 10). CONCLUSIONS: Single-stage combined hip arthroscopy with periacetabular osteotomy for patients with symptomatic hip dysplasia results in improvement in PROs and arthroplasty free survivorship of 92% at median 2.5 year follow-up. LEVEL OF EVIDENCE: Level IV, case series.

Magnetic Resonance Imaging Approximates Labral Width at the 9-, 12-, and 3-O'Clock Positions in the Setting of Revision Hip Arthroscopy.

PURPOSE: To compare preoperative magnetic resonance imaging (MRI) and intraoperative measurements of labral width and determine whether MRI can reliably predict labral width in the setting of revision surgery. METHODS: Patients who underwent revision hip arthroscopy with labral repair performed by a single surgeon from January 2008 to December 2015 were identified retrospectively from a prospectively collected database. The width of the labrum was measured intraoperatively at the time of surgery. Two orthopaedic surgeons performed labral width measurements on MRI scans at 3 standardized locations using the clock-face method. Interobserver and intraobserver reliabilities were calculated, and comparisons between intraoperatively measured labral widths and MRI measurements were performed. RESULTS: Fifty-eight patients who underwent revision hip arthroscopy were enrolled in the study. The average labral width measurements at the 3-, 12-, and 9-o'clock positions were 7.4 mm (standard deviation [SD], 1.2 mm), 7.5 mm (SD, 1.4 mm), and 6.6 mm (SD, 1.2 mm), respectively, on MRI compared with 6.7 mm (SD, 2.1 mm), 6.5 mm (SD, 2.5 mm), and 7.0 mm (SD, 1.9 mm), respectively, when measured intraoperatively. The average intraoperative measurements were smaller than the MRI measurements at the 3-o'clock (P = .03) and 12-o'clock (P = .01) positions. The inter-rater intraclass correlation coefficients between the 2 surgeons exhibited good agreement (0.612) at the 3-o'clock position, fair agreement (0.498) at the 12-o'clock position, and poor agreement (0.171) at the 9-o'clock position. The positive predictive values of the MRI measurements were 72% at the 3-o'clock position, 68% at the 12-o'clock position, and 88% at the 9-o'clock position for identifying a labral width of 6 mm or greater. CONCLUSIONS: The results of this study show that MRI-measured labral width and actual labral width measured at the time of revision arthroscopy are usually within 1 mm of each other. LEVEL OF EVIDENCE: Level II, diagnostic study investigating diagnostic test.

Adhesions in the setting of hip arthroscopy.

With the growing number of primary arthroscopies performed, patients requiring revision hip arthroscopies for various issues is high including postoperative adhesion formation, a source of pain, mechanical symptoms, range of motion limitation, stiffness, and microinstability. Adhesions are a consequence of biological pathways that have been stimulated by injury or surgical interventions leading to an increased healing response. Preventative efforts have included surgical adjuncts during/after primary hip arthroscopy, biologic augmentation, and postoperative rehabilitation. Treatment options for adhesion formation includes surgical lysis of adhesions with or without placement of biologic membranes aimed at inhibiting adhesion reformation as well as systemic medications to further reduce the risk. Postoperative rehabilitation exercises have also been demonstrated to prevent adhesions as a result of hip arthroscopy. Ongoing clinical trials are further investigating pathways and prevention of adhesion formation.

Biomechanical Comparison of Proximal Hamstring Reconstruction Using Distal Hamstring Graft Versus Fascia Lata Graft for Treatment of Chronic Hamstring Injury.

BACKGROUND: Surgical reconstruction using autografts is often required in treating chronic proximal hamstring injuries where the hamstring has retracted >5 cm. There is a paucity of evidence that evaluates reconstructive procedures using the 2 most popular autografts, distal hamstring and fascia lata. PURPOSE: To (1) compare failure load and elongation at failure between the proximal hamstring tendon reconstruction with distal hamstring and fascia lata grafts and (2) compare the stiffness between these reconstructions and the native state. STUDY DESIGN: Controlled laboratory study. METHODS: Seven pairs of human cadaveric hemipelvises (mean age, 60.4 ± 5.0 years; 6 male, 1 female) with no evidence of previous injury or abnormality were dissected to the proximal hamstring origin. Through use of a dynamic tensile testing system, each specimen underwent preconditioning followed by a distraction test to determine the native specimen stiffness. Each pair of specimens was assigned to undergo proximal hamstring reconstruction with distal hamstring and reconstruction with fascia lata. Each specimen then underwent preconditioning followed by pull to failure. The failure load, elongation at failure, mode of failure, and stiffness were determined for each repair. RESULTS: The distal hamstring group exhibited a greater failure load (mean, 334 ± 108 N; P = .031) and higher stiffness (mean, 47.6 ± 16.0 N/mm; P = .009) compared with the fascia lata group (mean, 179 ± 78 N and 23.0 ± 11.2 N/mm, respectively). Although the stiffness of the repair state in the distal hamstring group (mean, 61.4 ± 13.4 N/mm) was not significantly different from that of the native state (mean, 47.6 ± 16.0 N/mm), the stiffness of the repair state in the fascia lata group (mean, 23.0 ± 11.2 N/mm) was significantly lower than that of the native state (mean, 60.1 ± 17.7 N/mm) (P < .0001). The elongation at failure of the distal hamstring graft group (mean, 33.0 ± 6.6 mm) was not significantly different from that of the fascia lata graft group (mean, 29.2 ± 14.9 mm) (P = .58). The most common modes of failure for the distal hamstring group (29% each) were at the repair site, at the graft-muscle interface, and at the muscle, while the most common modes of failure for the fascia lata graft were at the tendon-graft interface. CONCLUSION: The distal hamstring group achieved higher failure load and stiffness than the fascia lata group, and stiffness of the distal hamstring group was not significantly different from that of the native tendon. Elongation at failure was not different between repair techniques. Although distal hamstring graft failure predominantly occurred in 3 distinct locations, failure of the fascia lata repair occurred predominantly at the tendon-graft interface. These cadaveric results suggest that it may be more clinically appropriate to use distal hamstring versus fascia lata for proximal hamstring reconstruction. CLINICAL RELEVANCE: Our time-zero study suggests that the proximal hamstring reconstruction with distal hamstring could be the preferred surgical treatment for chronic hamstring injury over reconstruction with fascia lata. The failure load of reconstruction with distal hamstring was inferior to that of primary suture anchor, suggesting that rehabilitation after reconstruction should not be more aggressive than the standard postoperative rehabilitation protocol for acute repair.

Therapeutic potential of senolytic agent quercetin in osteoarthritis: A systematic review and meta-analysis of preclinical studies.

BACKGROUND: Quercetin, a natural flavonoid, has shown promise as a senolytic agent for various degenerative diseases. Recently, its protective effect against osteoarthritis (OA), a representative age-related disease of the musculoskeletal system, has attracted much attention. The aim of this study is to summarize and analyze the current literature on the effects of quercetin on OA cartilage in in vivo preclinical studies. METHODS: The Medline (via/using PubMed), Embase, and Web of Science databases were searched up to March 10th, 2023. Risk of bias and the qualitative assessment including mechanisms of all eligible studies and a meta-analysis of cartilage histological scores among the applicable studies was performed. RESULTS: A total of 12 in vivo animal studies were included in this systematic review. A random-effects meta-analysis was performed on six studies using the Osteoarthritis Research Society International (OARSI) scoring system, revealing that quercetin significantly improved OA cartilage OARSI scores (SMD, -6.30 [95% CI, -9.59 to -3.01]; P = 0.0002; heterogeneity: I2 = 86%). The remaining six studies all supported quercetin's protective effects against OA during disease and aging. CONCLUSIONS: Quercetin has shown beneficial effects on cartilage during OA across animal species. Future double-blind randomized controlled clinical trials are needed to verify the efficacy of quercetin in the treatment of OA in humans.

Therapeutic Perspectives for Inflammation and Senescence in Osteoarthritis Using Mesenchymal Stem Cells, Mesenchymal Stem Cell-Derived Extracellular Vesicles and Senolytic Agents.

Osteoarthritis (OA) is the most common cause of disability worldwide among the elderly. Alarmingly, the incidence of OA in individuals less than 40 years of age is rising, likely due to the increase in obesity and post-traumatic osteoarthritis (PTOA). In recent years, due to a better understanding of the underlying pathophysiology of OA, several potential therapeutic approaches targeting specific molecular pathways have been identified. In particular, the role of inflammation and the immune system has been increasingly recognized as important in a variety of musculoskeletal diseases, including OA. Similarly, higher levels of host cellular senescence, characterized by cessation of cell division and the secretion of a senescence-associated secretory phenotype (SASP) within the local tissue microenvironments, have also been linked to OA and its progression. New advances in the field, including stem cell therapies and senolytics, are emerging with the goal of slowing disease progression. Mesenchymal stem/stromal cells (MSCs) are a subset of multipotent adult stem cells that have demonstrated the potential to modulate unchecked inflammation, reverse fibrosis, attenuate pain, and potentially treat patients with OA. Numerous studies have demonstrated the potential of MSC extracellular vesicles (EVs) as cell-free treatments that comply with FDA regulations. EVs, including exosomes and microvesicles, are released by numerous cell types and are increasingly recognized as playing a critical role in cell-cell communication in age-related diseases, including OA. Treatment strategies for OA are being developed that target senescent cells and the paracrine and autocrine secretions of SASP. This article highlights the encouraging potential for MSC or MSC-derived products alone or in combination with senolytics to control patient symptoms and potentially mitigate the progression of OA. We will also explore the application of genomic principles to the study of OA and the potential for the discovery of OA phenotypes that can motivate more precise patient-driven treatments.

A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury-A Pilot Case Series.

BACKGROUND: Senescence, a characteristic of cellular aging and inflammation, has been linked to the acceleration of osteoarthritis. The purpose of this study is to prospectively identify, measure, and compare senescent profiles in synovial fluid and peripheral blood in patients with an acute knee injury within 48 h. METHODS: Seven subjects, aged 18-60 years, with an acute ACL tear with effusion were prospectively enrolled. Synovial fluid and peripheral blood samples were collected and analyzed by flow cytometry, using senescent markers C12FDG and CD87. The senescent versus pro-regenerative phenotype was probed at a gene and protein level using qRT-PCR and multiplex immunoassays. RESULTS: C12FDG and CD87 positive senescent cells were detected in the synovial fluid and peripheral blood of all patients. Pro-inflammatory IL-1ß gene expression measured in synovial fluid was significantly higher (p = 0.0156) than systemic/blood expression. Senescent-associated factor MMP-3 and regenerative factor TIMP-2 were significantly higher in synovial fluid compared to blood serum. Senescent-associated factor MMP-9 and regenerative factor TGFß-2 were significantly elevated in serum compared to synovial fluid. Correlation analysis revealed that C12FDG++/CD87++ senescent cells in synovial fluid positively correlated with age-related growth-regulated-oncogene (ρ = 1.00, p < 0.001), IFNγ (ρ = 1.00, p < 0.001), IL-8 (ρ = 0.90, p = 0.0374), and gene marker p16 (ρ = 0.83, p = 0.0416). CONCLUSIONS: There is an abundance of senescent cells locally and systemically after an acute ACL tear without a significant difference between those present in peripheral blood compared to synovial fluid. This preliminary data may have a role in identifying strategies to modify the acute environment within the synovial fluid, either at the time of acute ligament injury or reconstruction surgery.

Losartan in Combination With Bone Marrow Stimulation Showed Synergistic Effects on Load to Failure and Tendon Matrix Organization in a Rabbit Model.

PURPOSE: To investigate the effects of combining bone marrow stimulation (BMS) with oral losartan to block transforming growth factor ß1 (TGF-ß1) on biomechanical repair strength in a rabbit chronic injury model. METHODS: Forty rabbits were randomly allocated into 4 groups (10 in each group). The supraspinatus tendon was detached and left alone for 6 weeks to establish a rabbit chronic injury model and was then repaired in a surgical procedure using a transosseous, linked, crossing repair construct. The animals were divided into the following groups: control group (group C), surgical repair only; BMS group (group B), surgical repair with BMS of the tuberosity; losartan group (group L), surgical repair plus oral losartan (TGF-ß1 blocker) for 8 weeks; and BMS-plus-losartan group (group BL), surgical repair plus BMS plus oral losartan for 8 weeks. At 8 weeks after repair, biomechanical and histologic evaluations were performed. RESULTS: The biomechanical testing results showed significantly higher ultimate load to failure in group BL than in group B (P = .029) but not compared with group C or group L. A 2 × 2 analysis-of-variance model found that the effect of losartan on ultimate load significantly depended on whether BMS was performed (interaction term F1,28 = 5.78, P = .018). No difference was found between the other groups. No difference in stiffness was found between any groups. On histologic assessment, groups B, L, and BL showed improved tendon morphology and an organized type I collagen matrix with less type III collagen compared with group C. Group BL showed the most highly organized tendon matrix with more type I collagen and less type III collagen, which indicates less fibrosis. Similar results were found at the bone-tendon interface. CONCLUSIONS: Rotator cuff repair combined with oral losartan and BMS of the greater tuberosity showed improved pullout strength and a highly organized tendon matrix in this rabbit chronic injury model. CLINICAL RELEVANCE: Tendon healing or scarring is accompanied by the formation of fibrosis, which has been shown to result in compromised biomechanical properties, and is therefore a potential limiting factor in healing after rotator cuff repair. TGF-ß1 expression has been shown to play an important role in the formation of fibrosis. Recent studies focusing on muscle healing and cartilage repair have found that the downregulation of TGF-ß1 by losartan intake can reduce fibrosis and improve tissue regeneration in animal models.

Timing From Symptom Onset to Hip Arthroscopy Does Not Affect Patient-Reported Outcome Measures for the Treatment of Femoroacetabular Impingement in Adolescent Patients.

PURPOSE: To evaluate symptom duration and its relationship to patient-reported outcomes (PROs) and survivorship after hip arthroscopy in adolescents. METHODS: Patients ≤18 at time of primary hip arthroscopy for femoroacetabular impingement (FAI) between January 2011 and September 2018 were included. Exclusion criteria consisted of history of previous ipsilateral hip surgery, presence of osteoarthritis or dysplasia on preoperative radiographs, previous hip fracture, or history of slipped capital femoral epiphysis or Legg-Calve-Perthes disease. Minimum 2-year PROs (modified Harris Hip Score, Hip Outcome Score [HOS]-Activities of Daily Living, HOS-Sport Scale, Short Forms 12 [SF-12]), minimum clinically significant difference (MCID) and patient-acceptable symptom state (PASS) rates, and revision surgery rates were compared based on symptom duration. RESULTS: Two-year minimal follow-up was obtained for 111 patients (134 hips) (80%), including 74 females and 37 males with a mean age of 16.4 ± 1.1 (range 13.0-18.0). The mean symptom duration was 17.2 ± 15.2 months (range 43 days to 6.0 years). Ten patients (11 hips), 6 females (7 hips) and 4 males, required revision surgery at an average of 2.3 ± 1.0 years (range 0.9-4.3 years). At a mean follow-up of 4.8 ± 2.2 years (range 2-10 years), there were statistically significant improvements in all PROs (P < .05 for all). Symptom duration showed no significant correlation to post-operative scores (correlation coefficient range -0.162 to -0.078, P > .05 for all). Symptom duration ≤12 months versus >12 months or as a continuous variable was not a predictor for requiring revision surgery or achieving MCID/PASS (95% confidence interval crosses 1 for all). CONCLUSIONS: In an adolescent cohort of symptomatic FAI patients who underwent hip arthroscopy, there is no difference in PRO measures when analyzing symptom duration by arbitrary time intervals or as a continuous variable. LEVEL OF EVIDENCE: Level IV, case series.

The Relationship Between the Joint Space and Outcomes After Hip Arthroscopic Surgery for Femoroacetabular Impingement: Reevaluating the 2-mm Rule.

BACKGROUND: A limited joint space (<2 mm) is associated with poorer outcomes and conversion to total hip arthroplasty (THA) after hip arthroscopic surgery. As indications for hip arthroscopic surgery expand, it is important to reevaluate established risk factors among large patient populations. PURPOSE: To reevaluate the relationship between the radiographic joint space and outcomes after hip arthroscopic surgery and to assess the validity of a joint space of 2 mm as the accepted cutoff for successful hip arthroscopic surgery. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients aged 18 to 50 years who underwent hip arthroscopic surgery for femoroacetabular impingement between January 2008 and December 2016 and had a minimum 2-year follow-up were included. Patients with previous ipsilateral hip surgery, a history of hip fractures, dysplasia (lateral center-edge angle <20°), or osteoarthritis (Tonnis grade >2) were excluded. The joint space was categorized as diminished (≤2 mm), borderline (>2 to ≤3 mm), or preserved (>3 mm). Minimum 2-year patient-reported outcomes (modified Harris Hip Score [mHHS], Hip Outcome Score-Activities of Daily Living [HOS-ADL], Hip Outcome Score-Sports-Specific Subscale [HOS-SSS]), revision rates, and rates of conversion to THA were compared between groups. RESULTS: A total of 699 patients (782 hips) with a mean age of 33.8 ± 10.1 years met 2-year inclusion criteria. The mean follow-up time was 4.2 ± 2.1 years. Overall, 51 hips (6.5%) had a diminished joint space, 297 (38.0%) had a borderline joint space, and 434 (55.5%) had a preserved joint space. Patients with a diminished joint space had larger femoral and acetabular defects compared with those with larger joint spaces. All groups had improved patient-reported outcome scores compared with baseline (P < .001 for all), and there were no differences between the groups in the percentage of patients who reached the minimal clinically important difference or patient acceptable symptom state. There were also no differences between the groups in revision rates (P = .95). A greater number of hips with a diminished joint space converted to THA (n = 8 [15.7%]) compared with those with a borderline (n = 9 [3.0%]) or preserved (n = 9 [2.1%]) joint space (P < .001). Considering joint space as a continuous variable, adjusted logistic regression showed that for every millimeter decrease in the joint space, the odds of conversion to THA increased by a factor of 2.5 (odds ratio, 2.5 [95% CI, 1.6-3.8]). CONCLUSION: This study demonstrated that patients with a diminished joint space were at a higher risk of conversion to THA. Although 2 mm should not serve as a strict cutoff, patients should be counseled based on their preoperative radiographic findings accordingly.

Improved Mental Health Status and Patient-Reported Outcomes After Hip Arthroscopy for Femoroacetabular Impingement.

BACKGROUND: Femoroacetabular impingement (FAI) is often a chronic problem, which can lead to a decrease in mental well-being. PURPOSE/HYPOTHESIS: The purpose of this study was to determine patient mental health improvement after hip arthroscopy and if this improvement correlated with improved outcomes. It was hypothesized that patients with low mental health (LMH) status would improve after hip arthroscopy for FAI and that their patient-reported outcomes (PROs) would significantly improve after surgery. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients who underwent hip arthroscopy with labral repair between 2008 and 2015 were included. The minimum follow-up was 2 years. PROs included the modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), HOS-Sports (HOS-Sports), and 12-Item Short Form Health Survey (SF-12). The minimal clinically important difference and Patient Acceptable Symptom State (PASS) were determined for HOS-ADL, HOS-Sports, and the mHHS based on previously published studies. Patients who scored <46.5 on the SF-12 Mental Component Summary (MCS) were in the LMH group, and those who scored ≥46.5 were in the high mental health (HMH) group. RESULTS: In total, 120 (21%) of the 566 patients were in the LMH group and 446 (79%) patients were in the HMH group preoperatively. There was no difference in age or sex between groups. Patients in the LMH group had lower mHHS, HOS-ADL, and HOS-Sports at the mean 4-year follow-up and were less likely to reach PASS for the scores. Postoperatively, 84% (478/566) of the entire group was in the HMH group. A total of 88 (73%) of the LMH group improved to HMH. A multiple linear regression model for change in MCS identified independent predictors of changes in preoperative MCS to be LMH group preoperatively, change in HOS-Sports, and change in mHHS (r2 = 0.4; P < .001). CONCLUSION: HMH was achieved in 84% of the patients after hip arthroscopy for FAI. Improvement in MCS was correlated with function and activity, as indicated by a significant correlation with HOS-ADL and HOS-Sports. A small percentage of patients did see a decline in their MCS score. This study showed that patients with LMH scores before hip arthroscopy for FAI can improve to normal/high mental health, and this correlated with higher PROs.

Sustained-release losartan from peptide nanofibers promotes chondrogenesis.

Introduction: The central pathologic feature of osteoarthritis (OA) is the progressive loss of articular cartilage, which has a limited regenerative capacity. The TGF-ß1 inhibitor, losartan, can improve cartilage repair by promoting hyaline rather that fibrous cartilage tissue regeneration. However, there are concerns about side effects associated with oral administration and short retention within the joint following intra-articular injections. To facilitate local and sustained intra-articular losartan delivery we have designed an injectable peptide amphiphile (PA) nanofiber that binds losartan. The aims of this study are to characterize the release kinetics of losartan from two different PA nanofiber compositions followed by testing pro-regenerative bioactivity on chondrocytes. Methods: We tested the impact of electrostatic interactions on nanostructure morphology and release kinetics of the negatively charged losartan molecule from either a positively or negatively charged PA nanofiber. Subsequently, cytotoxicity and bioactivity were evaluated in vitro in both normal and an IL-1ß-induced OA chondrocyte model using ATDC5. Results: Both nanofiber systems promoted cell proliferation but that the positively-charged nanofibers also significantly increased glycosaminoglycans production. Furthermore, gene expression analysis suggested that losartan-encapsulated nanofibers had significant anti-inflammatory, anti-degenerative, and cartilage regenerative effects by significantly blocking TGF-ß1 in this in vitro system. Discussion: The results of this study demonstrated that positively charged losartan sustained-release nanofibers may be a novel and useful treatment for cartilage regeneration and OA by blocking TGF-ß1.